International Journal of Trend in Scientific Research and Development (IJTSRD)
Volume: 3 | Issue: 2 | Jan-Feb 2019 Available Online: www.ijtsrd.com e-ISSN: 2456 - 6470
A Review on Genetic Dominant Disorder-Polydactyly
Akshata. B. Kichadi1, Dr. Uma B Gopal2, Santhosh Singarapu1,
Chaitra. S1, Manukrishnan. K1, Jeevankumar. Giri1
Scholars, 2Professor
Department of Rachana Shareera, SDM College of Ayurveda and Hospital, Hassan, India
1PG
ABSTRACT
Polydactyly is genetic disorder in which there is mutation of gene that is located on short arm of chromosome 7. One gene that
can cause polydactyly is GLI3 and it is one among number of genes that are known to be involved in the patterning of tissues &
organs during development of the embryo. Mutations of GLI3 gene during development will cause two types of polydactyly.
Those are postaxial(ulnar) and preaxial(radial) polydactyly.
The treatment plan is based on the outcome of analysis of patient’s medical history, social history, motivation, social and
psychological disturbance.
KEYWORDS: Mutations, gene, postaxial, preaxial, polydactyly
INTRODUCTION
A genetic disorder is a genetic problem caused by one or
more abnormalities in genome, especially a condition that is
present from birth. Genetic disorders may be hereditary,
passed down from the parents' genes1. In genetic disorders,
defects may be caused by new mutations or changes in DNA
sequence. In such cases, the defect will only be passed down
if it occurs in the germ line. Polydactyly is one such genetic
disorder in which, the mutation of gene that is located on
short arm of chromosome 7 is seen. One gene that can cause
polydactyly is GLI3 and it is one among number of genes that
are known to be involved in the patterning of tissues and
organs during development of the embryo. It does this by
helping to control whether specific genes are turned on or
off. That is because GLI3 is a transcriptional repressor, which
means that it codes for protein (in fact a DNA-binding
protein) that regulates the expression of one or several
genes by decreasing the rate of transcription. Mutations of
GLI3 gene during development are known to cause two types
of polydactyly4. Those are preaxial and postaxial polydactyly.
Development of limb usually takes places proximodistally,
once positioning along the craniocaudal axis is determined,
growth must be regulated along the proximodistal,
anterioposterior, and dorsoventral axis.It is initiated by
TBX5 and FGF10 in the forelimb and TBX4 and FGF10 in the
hindlimb secreted by lateral plate mesodermal cells.
Fig .1: postaxial polydactlyly of both hands
Fig.2:
CASE REPORT
A foetal specimen of polydactyly present in the museum of
department of Rachana Shareera, Sri Dharmasthala
Manjunateshwara College of Ayurveda & Hospital, Hassan
was selected for observational study.
Specimen: A male foetus showed postaxial or ulnar
polydactlyly in both hands
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International Journal of Trend in Scientific Research and Development (IJTSRD) @ www.ijtsrd.com eISSN: 2456-6470
Fig.3:
There are three types of classification of polydactyly they are
preaxial or radial,postaxial or ulnar and central. Among them
preaxial is most common, refers to duplication of first digital
rays.4
The foetal specimen found in museum of department of
rachana shareer, SDMCA & H,Hassan it was found that the
male foetus had postaxial polydactyly of both upper limbs.
DISCUSSION
Polydactyly follows an autosomal dominant pattern of
inheritance which means that
It is not sex linked, so that boys and girls may be equally
affected and
A child who has polydactyly parent has 50% chance of
being polydactyly .
As per routine observation done in museum of department
of Rachana Shareera ,SDMCA & H,Hassan it was found that
the male foetus had postaxial polydactyly of both upper
limbs.
Polydactyly is the most common congenital anomaly of hand
and foot. Embryologically Limb development begins with
the activation of a group of a mesenchymal cells in the lateral
plate mesoderm. It is said that a specialized gene called
homeobox gene regulate the pattern in the formation of
limb2. They start forming at the second month of
intrauterine life.
At the tip of each limb bud, the ectoderm is thickened to
form the apical ectodermal ridge(AER). This ridge has an
inducing effect on underlying mesenchyme causing it to
remain undifferentiated and to proliferate, the progress
zone. Areas away from the apical ridge undergo
differentiation into cartilage, muscles, etc. In this manner
,development of the limb proceeds proximodistally.3
The forelimb bud appear a little earlier than the hindlimb
buds. In 6 week old embryos, the terminal portion of the limb
buds becomes flattened to form the hand and footplates and
is separated from the proximal segment by a circular
constriction.6 As each forelimb bud grows, it becomes
subdivided by constrictions
into arm, forearm and hand. The hand itself soon shows
outline of digits. The interdigital areas show cell death
because of which the digits separate from each other. Similar
changes occur in hindlimbs. While the limb buds are
growing, the mesenchymal cells in the buds form
cartilaginous models, which subsequently ossify to form the
bones of the limbs.
The limb buds are first directed forward and laterally from
the body of the embryo. Each bud has preaxial border and
postaxial border. The thumb and the great toe are formed on
the preaxial border.3 During the seventh week of gestation,
the limbs rotates in opposite directions. The upper limb
rotates 90 degree laterally, so that the extensor muscles lie
on the lateral and posterior surface, and the thumb lie
laterally whereas the lower limb rotates approximately 90
degree medially, placing the extensor muscles on the
anterior surface and the big toe medially.6Sometimes two
AER are formed on the limb bud. This results in formation of
super numerary limb3
Polydactyly is reported to occur in 1 in every 500 live births
and hence it is not uncommon.5
Positioning of the limbs along the craniocaudal axis in the
flank region of the embryo is regulated by the HOX gene
expressed along this axis. These homeobox genes are
expressed in overlapping patterns from head to tail with
some having more cranial limits than others. For example,
the cranial limit of expression of HOXB8 is at the cranial
border of forelimbs, and misexpression of this gene alters
the position of limbs.
Once outgrowth is initiated, bone morphogenetic
proteins(BMPs), expressed in ventral ectoderm, induce
formation of apical endodermal ridge(AER) by signalling
through the homeobox gene MSX2. Expression of radical
fringe, in the dorsal half of the limb ectoderm, restricts the
location of AER to the distal tip of the limbs. This gene
induces expression of SER2, a homologue of drosophilia
serrate, at the border between cells that are expressing
radical fringe and those that are not. It is at this border that
the AER is established. Formation of the border itself is
assisted by expression of engrailed-1 in ventral ectoderm
cells, because this gene represses expression of radical
fringe. After the ridge is established, it expresses FGF4 and
FGF8, which maintain the progress zone, the rapidly
proliferating population of mesenchyme cells adjacent to the
ridge. Distal growth of limb is then affected by this rapidly
proliferating cells under the influence of the FGF’s. As
growth occurs, mesenchymal cells at the proximal end of the
progress zone become farther away from the ridge and its
influence begin to slow down their division rates and
differentiation.
Patterning of the anteroposterior axis of the limb is
regulated by the zone of polarizing activity(ZPA), a cluster of
cells at the posterior border of the limb near the flank. These
cells produce retinoic acid (vitamin A), which initiates
expression of sonic hedgehog(SHH), a secreted factor that
regulates the anteroposterior axis.
Thus, for example, digits appear in the proper order, with the
thumb on the radial(anterior) side. As the limb grows, the
ZPA moves distal ward to remain in proximity to the
posterior border of the AER. Misexpression of retinoic acid
or SHH in the anterior margin of the limb containing a
normally expressing ZPA in the posterior border results in
mirror image duplication of limb structures.
@ IJTSRD | Unique Reference Paper ID - IJTSRD20232 | Volume – 3 | Issue – 2 | Jan-Feb 2019
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International Journal of Trend in Scientific Research and Development (IJTSRD) @ www.ijtsrd.com eISSN: 2456-6470
The dorsoventral axis is regulated by BMP’s in the ventral
ectoderm, Which induce expression of the transcription
factor EN1. In turn, EN1 represses WNT7a expression,
restricting it to the dorsal limb ectoderm. WNT7a is a
secreted factor that induces expression of LMX1, a
transcription factor containing a homeodomain, in the dorsal
mesenchyme. LMX1 specifies cells to be dorsal, establishing
the dorsoventral components. In addition, WTN7a maintains
SHH expression in the ZPA and therefore indicatly affects
anteroposterior patterning as well. These two genes are also
intimately linked in signalling pathways in Drosophilia, and
this interaction is conserved in vertebrates. In fact, all of the
patterning genes in the limb have feedback loops. Thus,
FGF’s in the AER activate SHH in the ZPA, while WNT7a
maintains the SHH signal.
Although patterning genes for the limbs axes have been
determined, it is the HOX genes that regulate the types and
shapes of the bones of the limb. Thus, HOX gene expression,
which results from the combinatorial expression of
SHH,FGFs, AND WNT7a, occurs in phases in three places in
the limb that correspond to formation of the
proximal(stylopod), middle(zeugopod), and distal(autopod)
parts. Genes of the HOXA and HOXD clusters are the primary
determinants in the limb, and variations in their
combinatorial patterns of expression may account for
differences in forelimb and hindlimb structures. Just as in the
craniocaudal axis of the embryo, HOX genes are nested in
overlapping patterns of expression that somehow regulate
patterning. Factors determining forelimb versus hindlimb
are the transcription factors TBX5(forelimb) and TBX4
together with PITX1(hindlimbs)6.
CONCLUSION
Polydactyly is the most common congenital anomaly of the
hand and foot. The frequency of polydactyly varies widely
among populations. It may be an isolated condition or part of
a congenital syndrome. Polydactyly is generally classified
into three major groups: medial ray (preaxial), central ray
and lateral ray(postaxial).
The deformity is cosmetically unacceptable in many cultures
and this in turn leads to psychological burden. Polydactyly
often causes social embarrassment and results in
compromised to move the hand independently. It often has
severe impact on patients self-esteem and hampers his or
her quality of life. Hence the treatment plan is formulated
and tailored specifically for each individual patient. Though
evaluation and diagnosis are among most important aspects
of overall patient’s management, the treatment plan is based
on the outcome of analysis of patient’s medical history, social
history, motivation, social and psychological disturbances. A
patients ultimate satisfaction with treatment outcome often
depends upon attention to the patients’ chief concerns7.
In the dead foetal specimen mounted in museum of SDMCA
& H, Hassan, it was observed that the polydactyly was of post
axial or ulnar polydactyly in both upper limbs.
Radiographs of the affected limb are recommended to show
whether the rudimentary dgit contains skeletal elements.
The degree of deviation of the digit and the size of the
articulating metacarpal or metatarsal also may be helpful
and surgical planning.
REFERENCES
[1] https://en.m.wikipedia.org/wiki/Genetic_disorder.
[2] The developing human,clinically oriented embryology
,moore & persaud, 7th edition,pg-410.
[3] Human embryology,inderbir
edition,pg-122
singh,G.P
Pal,8th
[4] Left handed polydactyly: a case report, Nicola mumali
et all
[5] What causes polydactyl written by paul Arnold.edited
by paul Arnold.updated:8/29/2009,bright hub.
https://www.brighthub.com/science/genetics/articles
/47390.aspx
[6] Langman’s Medical embryology, T.W.Sadler,eleventh
edition,south Asian edition,published by wolters
Kluwer(india) pvt.ltd.,new delhi.chapter 9,pg 134-141
[7] Left handed polydactyly: a case report, Nicola mumali
et all.
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